Novel mutation (Gly280Ala) in the ATP-binding domain of glycerol kinase causes severe hyperglycerolemia.

K G Parhofer, J Otto, C Otto, T Wibmer

Journal: Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 2005;113(7):396-403

PMID: 16025401

Full Text on Georg Thieme Verlag Stuttgart, New York View on PubMed

Abstract

Glycerol kinase deficiency is a rarely diagnosed X-linked recessive disorder which occurs as a complex form together with the adrenal hypoplasia congenita (AHC) or with Duchenne muscular dystrophy (DMD) or as an isolated form either symptomatic or asymptomatic. We report the case of a male adult who had pseudo-hypertriglyceridemia (falsely elevated triglycerides of 552 mg/dl) refractory to lipid-lowering therapy for more than 15 years. Further investigations revealed an isolated, asymptomatic glycerol kinase deficiency. Using polymerase chain reaction and direct DNA sequencing, a novel missense mutation Gly280Ala in the Xp21.3 glycerol kinase gene was found. Comparison between human and E.coli glycerol kinase showed that the mutation affects a highly conserved amino acid in an ATP-binding domain in the active centre. This mutation is assumed to destabilize a hydrogen bond between ligand and enzyme resulting in a reduced activity of glycerol kinase and therefore in hyperglycerolemia.

Address: Physiological Chemistry, Adolf Butenandt Institute, University of Munich, Germany.

DOI: 10.1055/s-2005-865723

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MeSH Terms: Aged, Amino Acid Sequence, Carbohydrate Metabolism, Inborn Errors, DNA, Fatal Outcome, Female, Glycerol, Glycerol Kinase, Humans, Male, Models, Molecular, Molecular Sequence Data, Mutation, Missense, Pedigree, Polymerase Chain Reaction, Sequence Alignment, Triglycerides